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Highlights

Combination hormones for menopause don't reduce CHD risk

Estrogen plus progestin therapy does not reduce coronary heart disease risk during the first three to six years of use in women who started therapy close to menopause, researchers said.

Combination hormone replacement therapy increases the risk for coronary heart disease (CHD) in postmenopausal women, but this effect might be limited to the first years of use and to women who start therapy late in menopause. To examine these variables, researchers stratified the risks over time and reported their results in the Feb. 15 Annals of Internal Medicine.

Among women within 10 years of menopause at randomization, 2,782 were randomized to hormone therapy and 2,712 were randomized to placebo. Thirty-one CHD cases (14 in the first two years) occurred among those in the hormone group compared with 34 cases (12 in the first two years) in the placebo group.

During follow-up, 188 CHD cases (80 in the first two years) occurred in the 8,506 women assigned to hormone therapy compared with 147 cases (51 in the first two years) in the 8,102 women assigned to placebo. Compared with no use of hormone therapy, the hazard ratio for continuous use of estrogen plus progestin therapy was 2.36 (95% CI, 1.55 to 3.62) for the first two years and 1.69 (CI, 0.98 to 2.89) for the first eight years. For women within 10 years after menopause, the hazard ratios were 1.29 (CI, 0.52 to 3.18) for the first two years and 0.64 (CI, 0.21 to 1.99) for the first eight years.

The CHD-free survival curves for continuous use and no use of combination therapy crossed at about six years (CI, two years to 10 years), the point at which researchers described a possible cardioprotective effect in women who began therapy closer to menopause.

Limitations include that the analysis may not have fully adjusted for adherence and CHD risk. Also, sample sizes for some subgroup analyses were below the typical level of statistical significance. Further, the study did not address clinical and public health issues of hormone therapy or risk-benefit considerations, but instead focused on the effect of one common formulation of estrogen plus progestin therapy on CHD.

CVD risk higher in patients with migraines, study finds

Patients with migraines, especially migraines with aura, could be at greater risk for cardiovascular disease, according to a new study.

Researchers used data from the American Migraine Prevalence and Prevention study to examine the rate of diagnosis of cardiovascular disease (CVD) and CVD risk factors in patients with migraine (n=6,102) and patients without (n=5,243). Migraine diagnosis, treatment, and comorbid conditions, as well as CVD events, were determined via a mailed screening questionnaire. Case-patients with migraine were more likely to be women and of lower income than controls, while controls were younger than case-patients. The results of the study were published online Feb. 10 by Neurology.

The authors found an association in unadjusted analyses between migraine and migraine with aura and myocardial infarction, stroke and claudication; migraine without aura was associated with myocardial infarction and claudication but not stroke. Patients with migraine were more likely than those without to have diagnosed diabetes (12.6% vs. 9.4%; odds ratio [OR], 1.4; 95% CI, 1.2 to 1.6), hypertension (33.1% vs. 27.5%; OR, 1.4; 95% CI, 1.3 to 1.6), and high cholesterol levels (32.7% vs. 25.6%; OR, 1.4; 95% CI, 1.3 to 1.5). Migraine with and without aura was associated with higher Framingham risk scores. In analyses adjusted for sex, age, disability, treatment and CVD risk factors, migraine was associated with myocardial infarction (OR, 2.2; 95% CI, 1.7 to 2.8), stroke (OR, 1.5; 95% CI, 1.2 to 2.1), and claudication (OR, 2.69; 95% CI, 1.98 to 3.23).

The study had several limitations, including reliance on questionnaire data rather than clinical examination. However, the authors concluded that migraine is associated with CVD and its risk factors, although they noted that the increased risk, while statistically significant, may not be clinically relevant. An accompanying editorial also noted the limitations of the study but said that its strengths, including its large representative sample, largely make up for them. "Patients with migraine, in particular those with aura, should be investigated for vascular risk factors and be counseled how to treat them," the editorialists wrote.

Test yourself

A 65-year-old man is evaluated for hypoalbuminemia, hyperlipidemia, and slowly progressive proteinuria that have developed over 1 year. One year ago, he underwent squamous-cell lung cancer resection.

On physical examination, blood pressure is 150/90 mm Hg. Cardiac examination reveals a normal S1 and S2 without rubs or gallops. Pulmonary examination shows decreased breath sounds in the right lower lobe consistent with his previous surgery. Abdominal examination is normal. There is 3+ edema of the lower extremities.

Breast cancer

Antidepressant may weaken effect of tamoxifen in patients with breast cancer

The selective serotonin reuptake inhibitor paroxetine may inhibit the effectiveness of tamoxifen when the drugs are coprescribed in patients with breast cancer, according to a new study.

Tamoxifen, a drug that requires bioactivation by cytochrome P450 2D6 (CYP2D6), is commonly prescribed to treat estrogen-receptor positive breast cancer. Patients with breast cancer are also frequently prescribed antidepressants, either to treat depression or to mitigate the hot flushes associated with tamoxifen treatment. Selective serotonin reuptake inhibitors (SSRIs), however, are known to inhibit CYP2D6. Canadian authors performed a population-based cohort study to determine whether SSRIs lessen tamoxifen's effectiveness in women with breast cancer who are prescribed both drugs.

The authors looked at 2,430 women from Ontario, Canada, who were at least 66 years old, had been treated with tamoxifen for breast cancer between 1993 and 2005, and had received concomitant treatment with an SSRI. Most women were prescribed paroxetine (25.9%), followed by sertraline (22.3%), citalopram (19.2%), venlafaxine (15.0%) fluoxetine (10.4%) and fluvoxamine (7.2%). Seven hundred thirty-five patients received one or more non-SSRI antidepressants. By the end of follow-up (mean, 2.38 years; SD 2.59), 1,074 women (44.2%) had died, 374 (15.4%) of breast cancer. Patients whose use of tamoxifen overlapped with use of the SSRI paroxetine were more likely to die of breast cancer than those who had no such overlap; similar risk was not seen with other SSRIs. The study results were published online Feb. 8 by BMJ.

The authors noted that they were unable to determine the reason for antidepressant treatment and had no information on patients' breast cancer stage. However, their findings have strong implications for clinical practice, they wrote, because of the frequent use of combination therapy in women with breast cancer. They concluded that antidepressant choice can have a significant effect on survival in women with breast cancer who are taking tamoxifen, calling the drug interaction "extremely common, widely underappreciated and uniformly avoidable." An accompanying editorial noted that "a switch to an antidepressant with low or no CYP2D6 inhibitory activity should be considered in patients who are already treated with tamoxifen and paroxetine or fluoxetine." However, the editorialists cautioned that fluoxetine and paroxetine treatment should not be abruptly stopped, and called for more study on the clinical effects of the interactions between these drugs and tamoxifen as well as replication of the current study's findings in other populations.

Thromboembolism

Patients with SVT may also have DVT

Many patients who present with superficial venous thrombosis also either have or soon develop venous thromboembolism, according to a new study.

The French cohort study included 844 patients who saw a vascular medicine specialist for a symptomatic superficial venous thrombosis (SVT) of the lower limbs that was at least 5 cm on compression ultrasonography. At the first visit, 24.9% of the patients were found to also have a deep venous thrombosis (DVT) or symptomatic pulmonary embolism. Over three months of follow-up, 10% of the remaining patients developed thromboembolic complications, even though 90% of them received anticoagulants.

Patients who were male, had a history of DVT or pulmonary embolism, had previous cancer, or no varicose veins--risk factors that have been confirmed by other studies--were at higher risk of complications during follow-up. This study was limited by a premature termination of enrollment with only about half the patients originally called for. The results were published in the Feb. 16 Annals of Internal Medicine.

The findings show that SVT is not entirely benign, study authors concluded. Clinicians should consider using compression ultrasonography in SVT patients as well as watching for symptoms of pulmonary embolism (and testing when symptoms are spotted) and following up closely with all of these patients, the researchers said. They also called for more research into the benefits and risks of using systemic anticoagulant therapy to treat SVT and prevent DVT.

Mental health

Proposed updates for DSM-5 released

The American Psychiatric Association last week released proposed diagnostic criteria for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The revisions, which are open to public comment until April 20, were developed by 13 work groups and include changes such as:

Elimination of the diagnostic category of substance dependence. Both substance abuse and dependence will fall under a new category of "addiction and related disorders."

New suicide scales, which include research-based criteria, to help identify individuals most at risk.

A new category of "behavioral addictions," in which gambling will be the only disorder. Internet addiction was considered for this category, but found to be insufficiently researched.

A single category of "autism spectrum disorders" to include autistic disorder, Asperger's disorder, childhood disintegrative disorder and pervasive developmental disorder.

A change from the term "mental retardation" to "intellectual disability."

A new "risk syndromes" category to identify earlier stages of mental disorders, including dementia.

Changes in definitions of some eating disorders to emphasize development in adults.

Addition of "dimensional assessments" to diagnostic evaluations to take into account the severity of symptoms and cross-cutting symptoms (such as insomnia or anxiety) that occur across different diagnoses.

After public comments are collected, the new criteria will undergo review and refinement, including field trials, over the next two years. The changes can be viewed and comments submitted at the DSM-5 Web site. The final DSM-5 is expected to be released in May 2013, according to a press release. The last edition of the DSM was published in 1994.

FDA update

Rosuvastatin approved for patients without heart disease

Last week the FDA approved the cholesterol-lowering medication rosuvastatin (Crestor) for some patients who are at increased risk of heart disease but have not been diagnosed with it.

The drug's new approval now includes men 50 years of age and older and women 60 years of age and older who have an elevated level of high-sensitivity C-reactive protein (CRP) and at least one additional traditional cardiovascular risk factor such as smoking, high blood pressure, a family history of premature heart disease, or low amounts of HDL cholesterol.

The new indication is intended to reduce the likelihood of a heart attack or stroke or the need for a procedure to treat blocked or narrowed arteries in patients who have never been diagnosed with heart disease but are at increased risk of a cardiac event, according to an FDA press release. The approval, which was based on the results of JUPITER, does not support use in patients who have an elevated high-sensitivity CRP but no traditional cardiovascular risk factors.

AED, IV equipment recalled

The FDA announced recalls of automated external defibrillators and intravenous access devices last week.

Several AEDs have been recalled by manufacturer Cardiac Science Corp because the devices may not be able to deliver therapy during a cardiac resuscitation attempt. The affected machines were manufactured or serviced between Oct. 19, 2009 and Jan. 15, 2010 and include the following models: Powerheart 9300A, 9300E, 9300P, 9390A, 9390E, CardioVive 92532 and CardioLife 9200G and 9231. Each affected AED should immediately be removed from service since it may not deliver the expected therapy, the FDA said.

Certain lots of BD Q-Syte Luer Access Devices have been recalled because they may cause an air embolism or leakage of blood or therapeutic product. The device, a needleless valve, is intended for use with other infusion therapy products in the administration of fluids into the intravenous system. The affected lots were distributed from November 2008 through November 2009.

Education

ICD-10 summit to be held in April

The American Health Information Management Association's second annual ICD-10 summit will be held April 12-13, 2010, in Washington, D.C.

The Annual ICD-10 Summit is the primary source for information, education and resources for preparedness and strategic implementation guidance. In 2010, the summit will explore the challenges and opportunities of the transition to the ICD-10-CM/PCS coding systems and the 5010 HIPAA transaction, featuring respected and well-known speakers, experts, industry leaders, and practitioners from all health care settings. ACP is a collaborating organization for this event. For more information, visit the summit Web site or AHIMA's set of ICD10 resources.

Internal Medicine 2010

ACP Job Placement Center calls for physician profiles

Physicians looking for a new job may submit a profile to the ACP Job Placement Center, a service available at Internal Medicine 2010 in Toronto, Canada. The center, located in the Metro Toronto Convention Centre's Exhibit Hall, Booth 222, provides physicians with tools to assist in job searching as well as the opportunity to meet with potential employers.

Physician profiles are distributed to numerous employers participating in Internal Medicine 2010, which will be held April 22-24. After reviewing a profile, a recruiter may contact the physician to schedule a private on-site interview at the Convention Centre. Profiles can be submitted online.

From the College

ACP supports First Lady and HHS in childhood obesity initiative

ACP has issued a letter of support to President Obama, the First Lady, the U.S. Department of Health and Human Services (HHS), the U.S. Department of Education, and the U.S. Department of Agriculture for their efforts in launching a new initiative to reduce rates of overweight and obese children and adolescents. The letter is available online.

Cartoon caption contest

Put words in our mouth

ACP InternistWeekly wants readers to create captions for this cartoon and help choose the winner. Pen the winning caption and win a $50 gift certificate good toward any ACP product, program or service.

E-mail all entries to acpinternist@acponline.org. ACP staff will choose three finalists and post them online for an online vote by readers. The winner will appear in an upcoming edition.

This patient most likely has membranous nephropathy. Suspicion for this condition is raised in patients older than 55 years of age. The presence of a slowly progressive nephrotic syndrome suggests the possibility of solid tumor-associated membranous nephropathy. In a patient with a history of squamous-cell lung cancer and a new lung nodule in the left upper lobe that may represent recurrent cancer, the association between membranous nephropathy and a solid tumor of the lung is highly likely.

Minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy are all causes of the nephrotic syndrome. However, membranous nephropathy is most frequently associated with solid tumors. IgA glomerulonephritis and antineutrophil cytoplasmic autoantibody–associated small-vessel vasculitis are unlikely in the absence of hematuria on urinalysis. Similarly, neither of these conditions would be associated with a urinary protein excretion of 15 g/24 h.

Test yourself

A 24-year-old woman undergoes routine evaluation. She is pregnant at 12 weeks' gestation. Medical history is notable for homozygous sickle cell anemia (Hb SS). She has had multiple uncomplicated painful crises treated at home with hydration, nonopioid analgesia, and incentive spirometry. Following a physical exam and lab studies, what is the most appropriate management?

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